kuliah gagal jantung
TRANSCRIPT
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Preload
contractility
Afterload
Left ventricular size
Myocardial fibershortening
Heart rate
Arterial
Pressure
stroke volume
Peripheral
Resistance
CardiacOutput
Skema Komponen Komponen Penentu Aktivitas Jantung
Dikutip dari : Harrisons Internal Medicine ed.12 Vol.I
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Causes of Heart FailureCauses of Heart Failure
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Exacerbating orExacerbating orPrecipitating Factors of HFPrecipitating Factors of HF
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Kerusakan katup
Gagal jantung kronikRemodeling ventrikel kiri &
disfungsi kronik ventrikel kiri
Edema paru akut
Kerusakan myokard
Disfungsi ventrikel kiri
akut
ToksinVirusIskemiaHipertensi
Dispnea
Lelah
Edema
Hospitalisasi
Kematian
Penyebab Dasar & Manifestasi Gagal Jantung
Dikutip dari : Clinical Pharmacology, 4 th ed., Melmon and Morellis, 2000
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curah jantung
suplai darah ginjal
curah jantung(via kompensasi)
remodelling
Angiotensin II
sekresi renin
afterload preload frekuensi denyut
aktivitas simpatis
Firingsinus karotis
kontraktilitas
Respons Kompensasi Selama Kegagalan Jantung Kongestif
Dikutip dari : Basic & Clinical Pharmacology, 8 th ed., Katzung, 2001
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Spironolacton
AT antagonis
ACE-I
Vasodilator
preload afterloadLipid modulatorObat anti diabetes
InsulinIHD
Anti iskemia
PG
NO
BK
Vasodilatasi Inaktif
AI
AII
Kerusakan
myokard
Disfungsi
jantung
Otak
NE
Digoxin
AVPAldosterone vasokonstriksi Stress oksidatif Stimulasi myokard
Retensi air Retensi
garam
Worsening HFDisfungsi endothel
Sitokin Neurohormon
tanda & gejala kualitas hidup, lama perawatan RS Kematian akibatkegagalan pompajantung
Kematian akibat
aritmia ventrikel
Faktor resiko :
Diabetes,
dislipidemia
performa jantung
blockerAntioksidan-blocker
ACE-I, -blocker, diuretic,
digoxin, nitrat
ACE-I, -blockerTransplantasi
Hipertensi
amiodarone
Antihipertensi
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Terapi Gagal Jantung Sistolik
Berikan diuretika untuk mencapaiuevolemia
Tambahkan ACE inhibitor
Tidak toleran terhadap ACEinhibitor
Toleransi baik terhadap ACE inhibitor
TambahkanARB
Tambahkan - blocker, lakukan titrasidosis
Tambahkan - blocker
Tidak toleran terhadap - blocker
Toleransi baikterhadap - blocker
Tidak toleran
terhadap - blocker
Toleransi baik
terhadap - blocker
Lanjutkan terapi dengan
diuretika, ARB, dan - blocker
Lanjutkan terapi dengan
diuretika & - blocker,pertimbangkanpenambahanspironolakton
Tambahkan ARBatauspironolakton
Lanjutkan terapi dengandiuretika, ACE inhibitordan - blocker(memiliki bukti efikasipaling besar)
Lanjutkan terapi dengan
diuretika, ACE inhbitor dan ARBatau spironolakton
Dikutip dari : Finding The Optimal Combinationtherapy, Cleveland Clinic Journal of Medicine, Vol.69,2002
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Angiotensin Converting Enzyme Inhibitors Commonly Used for Chronic Heart Failure Treatment
DRUGUSUAL
STARTINGDOSE (mg)
DOSERANGE
TIMETO
ONSET(H)
PEAKEFFECT
(H)
T1/2 (H) PRODRUG
ROUTE OFELIMINATION
Captopril 6.25 6.25 50 mgtid
0.3 1 2 N Renal
Enalaprilmaleate
2.5 2.5 bid 1 4 6 11 Y Renal
Lisinopril 2.5 5 35mg/day 1 4 6 13 N Renal
Ramipril 2.5 5 10 mgbid
1 2 3 6 12 Y R+H 70/30
Quinapril 5 10 20 mgbid
1 4 3 Y Renal
Trandolapril 1 1 4 mg/day 2 6 8 16 24 Y R+H 30/70
ABBREVIATION : R+H, renal + hepatic
Dikutip dari : Clinical Pharmacology, 4th ed., Melmon & Morellis, 2000
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Therapeutics classification of subsets in acute myocardial infarction
SubsetSystolic ArterialPressure (mmHg)
Left VentricularFilling Pressure
(mmHg)
Cardiac Index(L/min/m2)
Therapy
1. Hypovolemia < 100 20 > 2.5 Diuretics
3. Peripheral congestion < 100 10 20 > 2.5 None, or vasoactivedrugs
4. Power Failure < 100 > 20 < 2.5 Vasodilators, inotropicdrugs
5. Severe shock < 90 > 20 < 2.0 Vasoactivedrugs,inotropic drugs,vasodilators, circulatoryassist
6. Right ventricularinfarction
< 100 RVFP > 10LVFP < 15
< 2.5 Provide volumereplacement for LVFP,inotropic drugs, avoid
diuretics
7. Mitral regurgitation,ventricular septal defect
< 100 > 20 < 25 Vasodilators, inotropicdrugs, circulatory assist,surgery
The numerical values are intended to serve as general guidelines and not as absolute cutoff points. Arterial
pressures apply to patients who were previously normotensive and should be adjusted for patients who were
previously hypertensive.
(RVFP and LVFP = right and left ventricular filling pressure.)
Dikutip dari : Basic & Clinical Pharmacology, Katzung, 2001
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S
T
R
O
K
E
V
O
L
U
M
E
VENTRICULAR FILLING PRESSURE
Normal Congestive symptoms
Low output symptoms
I
D
I + V + DV
I + V
Respons Hemodinamik terhadap Intervensi Farmakologik pada Gagal Jantung
I : inotropic agent; V : vasodilator; D : diuretic
Dikutip dari : Pharmacological Basis of Therapeutics, Goodman & Gilmans, 10thed., 2001
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Penyebab Resistensi terhadap Diuretika pada Gagal Jantung
Dikutip dari : Pharmacological Basis of Therapeutics, 10th ed., Goodman & Gilmans, 2001
Ketidakpatuhan pada regimen terapi dan / atau asupan Na+ yang berlebihan pada diet
Penurunan perfusi ginjal dan laju filtrasi glomerulus akibat :
Deplesi volume intravaskuler yang berlebihan dan hipotensi akibat pemberian diuretika yang agresif dan / atau terapi
vasodilatorPenurunan curah jantung oleh karena makin memburuknya gagal jantung, aritmia atau oleh penyebab primer pada
jantung lainnya
Reduksi selektif pada tekanan perfusi glomeruler yang menyertai pemberian awal dan atau peningkatan dosis terapi
dengan ACE inhibitor
Obat obat antiinflamasi non steroid (NSAIDs)
Kelainan primer pada ginjal (misalnya, emboli kolesterol, stenosis arteri renalis, drug induced interstitial nephritis,
uropati obstruktif)
Penurunan atau gangguan absorpsi diuretika oleh karena edema dinding usus dan penurunan aliran darah
splannikus
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Bradykinin
Inactive
peptide
Nitric Oxide
Prostacyclin
Angiotensinogen
Angiotensin I
Renin
ACE inhibitors
ACE
(Kininase)
Non ACE dependent
patways, e.g., chymase
AT1 receptors AT2 receptors
AldosteroneVasoconstriction
Sympathetic stimulation
Cellular hypertrophy
Renovascular effects
AT1 receptor antagonist
Angiotensin II
Bradykinin
receptors
The renin angiotensin aldosterone systemDikutip dari : Pharmacological Basis of Therapeutics, Goodman & Gilmans, 10th ed., 2001
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OUTFLOW RESISTANCE
S
T
R
O
K
E
V
O
L
U
M
E
normal Hypertension
Myocardial dysfunction, moderate
Myocardial dysfunction,severe
Relationship between ventricular outflow resistance and stroke volume in patients with systolic ventricular
dysfunction
Dikutip dari : Pharmacological Basis of Therapeutics, Goodman & Gilmans, 10th ed., 2001
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Peran Potensial Aldosterone pada Patofisiologi Gagal Jantung
MEKANISMEEFEK PATOFISIOLOGI
Peningkatan retensi natrium Edema, peningkatan tekanan pengisian jantung
Peningkatan ekskresi kalium dan magnesium Aritmogenesis dan resiko henti jantung mendadak
Penurunan uptake norepinefrin dari myokard Potensiasi efek NE terhadap remodeling danaritmogenesis
Penurunan sensitivitas baroreseptor Penurunan aktivitas parasimpatis dan resiko hentijantung mendadak
Fibrosis myokard, proliferasi fibroblast Remodeling dan disfungsi ventrikel
Perubahan ekspresi kanal natrium Peningkatan eksitabilitas dan kontraktilitas otot jantung
Dikutip dari : Pharmacological Basis of Therapeutics, 10
th
ed., Goodman & Gilmans, 2001
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Obat obat Vasodilator yang Digunakan pada Terapi Gagal Jantung
ikutip dari : Pharmacological Basis of Therapeutics, 10th ed., Goodman & Gilmans, 2001
KELAS OBATCONTOH MEKANISME KERJA
VASODILATASIPENURUNAN
PRELOADPENURUNANAFTERLOAD
Nitrat Organik Nitroglycerin,
isosorbide dinitrate
Vasodilatasi yang diperantarai
oleh NO
+++ +
Donor Nitric Oxide (NO)
Nitroprusside Vasodilatasi yang diperantaraioleh NO
+++ +++
Angiotensin convertingenzyme inhibitors(ACEI)
Captopril,enalapril, lisinopril
Hambatan pembentukanangiotensin, penurunandegradasi bradykinin
++ ++
Angiotensin receptorblockers
Losartan,candesartan
Blockade reseptor angiotensin ++ ++
Phosphodiesteraseinhibitors
Milrinone,inamrinone
Hambatan degradasi cAMP ++ ++
Direct acting Hydralazine,minoxidil Tidak diketahui + +++
Subtype selective 1
adrenergic receptorantagonists
Doxazosin,prazosin Hambatan selektif reseptor1
+++ ++
Non subtype selective adrenergicreceptor antagonists
Phentolamine Hambatan non selektif reseptor
+++ +++
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Guidelines for Pharmacological Management of Ambulatory Patients with Heart Failure
NYHA Functional Class IMild HF
II III IV
Severe HF
Diuretics
ACE inhibitors
-receptor blockers
Consider use Consider use
Digoxin - atrial fibrillation
Digoxin - sinus rhythm Consider use
Spironolactone Consider use
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: Routinely used: Drugs should be consideredDikutip dari : Pharmacological Basis of Therapeutics, Goodman & Gilmans, 10th ed.,
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Classification & DrugTherapy of Heart Failure
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Treatment Algorithm for Chronic Heart Failure
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Outcome Evaluation of Chronic HF
Volume status
Exercise tolerance
Overall symptoms
Quality of Life (QoL)
Adverse drug reaction (ADR)
Disease progression & Cardiac function
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Acute Heart Failure
Hemodynamic category :
Volume status : Wet / dry
Wet volume/fluid overload
Dry EuvolemicEuvolemicPerfusion adequacy : Warm / cool
Warm adequate cardiac output (CO) to perfuse
peripheral tissues
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Clinical Presentation
Subset I (Warm&Dry)
Cardiac index (CI) > 2.2L/min/m2, pulmonary capillarywedge pressure (PCWP) < 18
mmHg
Patient considered wellcompensated & perfused,without evidence of congestion
No immediate interventionnecessary except optimizingoral medication & monitoring
Subset II (Warm&wet)
CI > 2.2 L/min/m2, PCWP 18 mmHg
Patients adequately perfused &shows signs & symptoms ofcongestion
Main goal is to reduce preload(PCWP) with loop diuretics
and vasodilators
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Subset III (Cool & Dry)
CI < 2.2L/min/m2, PCWP < 18mmHg
Patients are inadequately perfused& not congested
Hypoperfusion leads to increasedmortality, elevating death ratesfour-fold compared to those whoare adequately perfused
Treatment focuses on increasingCO with positive inotropic agentsand/or replacing intravascularfluids
Fluid replacement must beperformed cautiously, as patientscan rapidly become congested
Subset IV (Cool & wet)
CI < 2.2 L/minute per square meter,PCWP >18 mm Hg
Patients are inadequately perfusedand congested
Classified as the most complicatedclinical presentation of AHF with theworst prognosis
Most challenging to treat; therapytargets alleviating signs andsymptoms of congestion byincreasing CI as well as reducingPCWP, while maintaining adequate
mean arterial pressure
Treatment involves a delicate balancebetween diuretics, vasodilators, andinotropic agents
Use of vasopressors is sometimesnecessary to maintain blood pressure
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Usual Hemodynamic Effects of Commonly Used
Intravenous Agents for Treatment of Acute or Severe
Heart Failure
*Recombinant BNP
*